Presence and characteristics of receptors for [D-Trp6]luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer.
This study was undertaken to establish the presence and characteristics of receptors for [D-Trp6]LH-RH on the membranes of human ovarian cancer. Specific binding of [125I, D-Trp6]LH-RH was found in 29 of 37 (78.4%) ovarian cancers and in 6 of 11 (54.5%) non-malignant human ovaries. Ligand binding was dependent on time and plasma membrane concentration in a fashion expected of a peptide hormone. Saturation, kinetic and displacement data were consistent with the presence of a highly specific, single class of non-cooperative binding site. On the basis of receptors affinity, LH-RH-receptor-positive ovarian cancers could be divided into two groups: high affinity group (Kd=2.71 +/- 0.60 nM; Bmax=0.46 +/- 0.07 pmol/mg membrane protein) comprising 55% of tumors, and low affinity group (Kd=78.0 +/- 19.6 nM; Bmax=9.44 +/- 2.68 pmol/mg membrane protein) which included 45% of tumors. LH-RH antagonist Cetrorelix showed an affinity to LH-RH receptors on ovarian cancers 14 times higher than the agonist [D-Trp6]LH-RH. Using 125I-epidermal growth factor, specific high affinity receptors were also detected in membranes from 13 of 24 (54%) ovarian cancers and 5 of 11 (45%) non-malignant ovaries. The demonstration of LH-RH receptors in human ovarian cancers provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy. The probable involvement of growth factors in the development of ovarian cancers suggests the merit of trying a combined therapy based on analogs of LH-RH and somatostatin for this carcinoma.
Srkalovic
G
G
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA, USA.
Schally
A V
AV
Wittliff
J L
JL
Day
T G
TG
Jenison
E L
EL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011966:Receptors, LHRH / Q000032:analysis / Q000378:metabolism*; D017329:Triptorelin Pamoate / Q000378:metabolism
D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D066246:ErbB Receptors